Investigating the neural mechanisms of positive and negative social interactions

PROJECT SUMMARY Mood disorders like major depression are leading contributors to disease burden worldwide. Depression can cause a wide range of symptoms affecting arousal, motivation, mood, and cognition. Unfortunately, current treatment strategies are only effective for a subset of patients. While any individual can develop impairments in these domains of function, there are known risk and protective factors that modify one’s vulnerability. Negative social experiences like bullying are associated with increased risk, while having positive social support is a known protective factor. However, the underlying mechanisms by which these risk and protective factors lead to enduring brain and behavioral changes and how they interact are unknown. To develop more effective therapeutic approaches for depression and related psychiatric disorders, it is necessary to have a more detailed understanding of the ways by which conserved neurobiological systems are altered by them. This proposal will utilize a mouse model of chronic social stress called Vicarious Social Defeat Stress to comprehensively characterize physiological, behavioral, and neural activity changes associated with negative social experiences through Aim 1. This model will then be used to investigate the role of a proposed neural circuit element in the stress ameliorating effects of positive social interactions, commonly referred to as social buffering in Aim 2. Preliminary data suggests the medial amygdala (MeA) is active during acute stress, which is particularly interesting given the various known social functions of this nucleus. Subsequent experiments will test the hypothesis that the MeA is involved in and required for social buffering. In Aim 2, fiber photometry will be used to monitor MeA neural activity dynamics during post-stress social interactions, which will be linked to physiological and behavioral outcomes. In Aim 3, chemogenetics will be used to inhibit the MeA during poststress social interactions followed by assessment of physiological and behavioral outcomes to determine its functional necessity in social buffering. These experiments will improve our understanding of how different social experiences interact to produce complex behavioral responses, laying the groundwork for future research to investigate the potential therapeutic applications of this knowledge.